Dr. Vamsidhar Velcheti

What if more patients with lung cancer could benefit from immunotherapy? As oncologists know, immunotherapy can be remarkably effective for certain patients with otherwise hard-to-treat lung cancers. Although progress in this area of research is exciting, unfortunately, a vast majority of patients do not respond to immunotherapy.

Vamsidhar Velcheti, MD, assistant professor of medicine at Cleveland Clinic, is trying to change this. Dr. Velcheti and his team have been investigating why some people respond to immunotherapy while others do not. They are using their findings to develop new techniques and treatment options for patients with lung cancer. This work has been made possible in part thanks to a 2012 Conquer Cancer Foundation (CCF) Young Investigator Award (YIA) and a 2015 CCF Career Development Award (CDA).

“Even though the new wave of immunotherapy drugs targeting the immune-checkpoint pathways represents a significant advance in the treatment of lung cancer, a majority of the patients do not benefit from these treatments,” Dr. Velcheti said. “Trying to understand how to select patients who could potentially benefit from these very exciting treatments has been a challenge in the field.”

Dr. Velcheti ‘s work funded by the 2012 CCF YIA helped with several projects that lead to our understanding of the differences in the immune landscape of lung cancer and how some lung cancers are more recognized by the body’s immune system than others.

Unfortunately, a majority of lung cancers are not able to mount an adequate immune response, and one of the key reasons why is suppression of critical proteins in the tumor that help the immune system recognize it. This makes the tumors invisible to the immune system, thereby making immunotherapy ineffective. Drugs such as decitabine can address this issue, but certain challenges often render it useless.

Fortunately, Dr. Velcheti and his team at the Cleveland Clinic and at the National Institutes of Health (NIH) have extensively studied drugs such as decitabine that can optimize immune checkpoint inhibitors. Dr. Velcheti and team identified the main challenge faced by decitabine and found a way to address it. In a phase I clinical trial, they showed that pairing decitabine with another drug called tetrahydrouridine makes decitabine much more effective.

This finding also has implications for helping boost nivolumab’s effectiveness. With the support of a 2015 CCF Career Development Award, Dr. Velcheti and his team are launching a phase II trial to determine whether a combination of nivolumab, decitabine, and tetrahydrouridine can increase the number of patients with non–small cell lung cancer who benefit from immunotherapy. This is a phase II multi-institutional clinical trial in collaboration with the NIH. The trial has the potential to help many patients and improve outcomes from treatment with immunotherapy; it also may never have taken place without the initial support of CCF donors who made Dr. Velcheti’s research possible.

Dr. Velcheti recalls the story of one patient in particular who inspired him to pursue this work. “When I was a fellow at Yale University, one of my patients, who is a high school teacher who had lung cancer, had multiple treatments that did not work. She came to us for treatment, went on an immunotherapy clinical trial, and had a remarkable response,” he said. “Thanks to this treatment, she’s had a prolonged duration of response for years.”

Improving patient care is at the heart of all that Dr. Velcheti does.

“Conquering cancer for me means hope for patients—offering new opportunities and prolonging their lives,” Dr. Velcheti said. “It’s an incredible feeling to be able to make an impact in someone’s life.”